Abstract
Transplantation of mesenchymal stromal cells (MSCs) is an emerging therapy for the treatment of heart failure. However, the delivery method of MSC is currently suboptimal. The use of self-assembling peptide hydrogels, including PuraMatrix® (PM; 3-D Matrix, Ltd), has been reported for clinical hemostasis and in research models. This study demonstrates the feasibility and efficacy of an advanced approach for MSC-therapy, that is coating of the epicardium with the instantly-produced PM hydrogel incorporating MSCs (epicardial PM-MSC therapy). We optimized the conditions/procedure to produce “instant” 2PM-MSC complexes. After spreading on the epicardium by easy pipetting, the PM-MSC complex promptly and stably adhere to the beating heart. Of note, this treatment achieved more extensive improvement of cardiac function, with greater initial retention and survival of donor MSCs, compared to intramyocardial MSC injection in rat heart failure models. This enhanced efficacy was underpinned by amplified myocardial upregulation of a group of tissue repair-related genes, which led to enhanced repair of the damaged myocardium, i.e. augmented microvascular formation and reduced interstitial fibrosis. These data suggest a potential for epicardial PM-MSC therapy to be a widely-adopted treatment of heart failure. This approach may also be useful for treating diseases in other organs than the heart.
Highlights
Transplantation of mesenchymal stromal/stem cells (MSCs) has been developed as a promising new approach for various diseases that are difficult to treat with current treatments, including graftversus-host disease, autoimmune diseases, and heart failure [1e3]
We have reported that epicardial placement of MSCs in the form of a “cell-sheet”, produced in temperature-responsive dishes markedly improved donor cell survival and amplified therapeutic effects compared to intramyocardial injection in rat models of acute Myocardial infarction (MI) and heart failure [17,18]
rat fetal membrane-derived MSCs (Rf-MSCs) were tested as a model of Ha-MSCs in human cases
Summary
Transplantation of mesenchymal stromal/stem cells (MSCs) has been developed as a promising new approach for various diseases that are difficult to treat with current treatments, including graftversus-host disease, autoimmune diseases, and heart failure [1e3]. In addition to their capacity for anti-inflammation and tissue repair, MSCs have an advantage as a potential donor for stem cell therapy in the utility for allogeneic cell transplantation. The use of autologous stem cells requires an invasive biopsy from the patient and takes protracted culture for expansion, and quality control of each cell product, which imposes significant logistic, economic, and timing constraints [5]. Adipose-tissue, fetal-membrane, amnion membrane, and cord blood are considered to be promising sources [6e9]
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